Selective expression of a stable cell surface molecule on type 2 but not type 1 helper T cells.
T helper cell type 1 (Th1) and 2 (Th2) are central to immune regulation. However, no stable cell surface marker capable of distinguishing and separating these two subsets of CD4(+) cells has yet been found. Using differential display PCR, we have identified a gene encoding a cell membrane bound molecule, originally designated ST2L, T1, DER4, or Fit, expressed constitutively and stably on the surface of murine Th2s, but not Th1s even after stimulation with a range of immunological stimuli. Antibody against a peptide derived from ST2L strongly and stably labeled the surface of cloned Th2s but not Th1s, and Th2s but not Th1s derived from naive T cells of ovalbumin T cell receptor-alpha/beta transgenic mice. Three-color single cell flow cytometric analysis shows that cell surface ST2L coexpressed with intracellular interleukin (IL)-4, but not with interferon (IFN)-gamma. The antibody selectively lysed Th2s in vitro in a complement-dependent manner. In vivo, it enhanced Th1 responses by increasing IFN-gamma production and decreasing IL-4 and IL-5 synthesis. It induced resistance to Leishmania major infection in BALB/c mice and exacerbated collagen-induced arthritis in DBA/1 mice. Thus, ST2L is a stable marker distinguishing Th2s from Th1s and is also associated with Th2 functions. Hence, it may be a target for therapeutic intervention.
Xu
D
D
Department of Immunology, University of Glasgow, Glasgow G11 6NT, United Kingdom.
Chan
W L
WL
Leung
B P
BP
Huang
F p
Fp
Wheeler
R
R
Piedrafita
D
D
Robinson
J H
JH
Liew
F Y
FY
D000818:Animals; D000945:Antigens, Differentiation, T-Lymphocyte / Q000235:genetics*; D001169:Arthritis, Experimental / Q000276:immunology; D001483:Base Sequence; D005260:Female; D005434:Flow Cytometry; D015870:Gene Expression; D018507:Gene Expression Regulation, Developmental; D007896:Leishmaniasis / Q000276:immunology; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008811:Mice, Inbred DBA; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D018417:Th1 Cells / Q000502:physiology*; D018418:Th2 Cells / Q000502:physiology*
D000945:Antigens, Differentiation, T-Lymphocyte; D012333:RNA, Messenger